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In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration
Open accessAbstract
The Wnt target gene Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) marks actively dividing stem cells in Wnt-driven, self-renewing tissues such as small intestine and colon, stomach and hair follicles. A three-dimensional culture system allows long-term clonal expansion of single Lgr5(+) stem cells into transplantable organoids (budding cysts) that retain many characteristics of the original epithelial architecture. A crucial component of the culture medium is the Wnt agonist RSPO1, the recently discovered ligand of LGR5. Here we show that Lgr5-lacZ is not expressed in healthy adult liver, however, small Lgr5-LacZ(+) cells appear near bile ducts upon damage, coinciding with robust activation of Wnt signalling. As shown by mouse lineage tracing using a new Lgr5-IRES-creERT2 knock-in allele, damage-induced Lgr5(+) cells generate hepatocytes and bile ducts in vivo. Single Lgr5(+) cells from damaged mouse liver can be clonally expanded as organoids in Rspo1-based culture medium over several months. Such clonal organoids can be induced to differentiate in vitro and to generate functional hepatocytes upon transplantation into Fah(-/-) mice. These findings indicate that previous observations concerning Lgr5(+) stem cells in actively self-renewing tissues can also be extended to damage-induced stem cells in a tissue with a low rate of spontaneous proliferation.
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“Liver organoids derived from leucine-rich repeat–containing G protein–coupled receptor 5 (LGR5)–positive liver progenitor cells (LPC) can be stably maintained for months and can differentiate into functionally competent hepatocytes and cholangiocytes [14–16].”
From High-throughput human microfluidic organoid-on-a-chip platform for modeling liver diseases and screening nanotherapeutics. (2026) · cites this paper as [14]
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“The liver organoid has selfrenewal capability, a key proliferative property for its long-term culture and clonal expansion from single cells with sustained stemness (Huch et al., 2013;Hu et al., 2018).”
From Fast formation and maturation enhancement of human liver organoids using a liver-organoid-on-a-chip (2024) · cites this paper as Huch et al., 2013
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“These studies demonstrated that HPCs arise within the liver, engraft the parenchyma14 and may have some differentiation capacity but did not regenerate significant quantities of liver parenchyma11-13.”
From Hepatic progenitor cells of biliary origin with liver repopulation capacity (2015) · cites this paper as [12]
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Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204
Self-citationIdentification of stem cells in small intestine and colon by marker gene Lgr5
Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687
Self-citationGeneralized lacZ expression with the ROSA26 Cre reporter strain
Soriano, P. (1999) · Nature Genetics · doi:10.1038/5007 · Cited by 5,237
Cell fusion is the principal source of bone-marrow-derived hepatocytes
Wang, X., Willenbring, H., Akkari, Y. M. N., Torimaru, Y., Foster, M., Al-Dhalimy, M., Lagasse, E., Finegold, M. J., Olson, S. B., & Grompe, M. (2003) · Nature · doi:10.1038/nature01531 · Cited by 1,569
Self-citationLgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro
Barker, N., Huch, M., Kujala, P., van de Wetering, M., Snippert, H. J., van Es, J. H., Sato, T., Stange, D. E., Begthel, H., van den Born, M., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2009.11.013 · Cited by 1,547
Self-citationLgr5 homologues associate with Wnt receptors and mediate R-spondin signalling
de Lau, W., Barker, N., Low, T. Y., Koo, B., Li, V. S. W., Teunissen, H., Kujala, P., Haegebarth, A., Peters, P. J., van de Wetering, M., et al. (2011) · Nature · doi:10.1038/nature10337 · Cited by 1,302
Self-citationLustig, B., Jerchow, B., Sachs, M., Weiler, S., Pietsch, T., Karsten, U., van de Wetering, M., Clevers, H., Schlag, P., Birchmeier, W., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1184-1193.2002 · Cited by 1,198
Self-citationLgr5 marks cycling, yet long-lived, hair follicle stem cells
Jaks, V., Barker, N., Kasper, M., van Es, J. H., Snippert, H. J., Clevers, H., & Toftgård, R. (2008) · Nature Genetics · doi:10.1038/ng.239 · Cited by 966
Self-citationCarmon, K. S., Gong, X. W., Lin, Q., Thomas, A., & Liu, Q. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1106083108 · Cited by 894
Furuyama, K., Kawaguchi, Y., Akiyama, H., Horiguchi, M., Kodama, S., Kuhara, T., Hosokawa, S., Elbahrawy, A., Soeda, T., Koizumi, M., et al. (2010) · Nature Genetics · doi:10.1038/ng.722 · Cited by 841
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Guo, Q., Chen, S., Rao, X., Li, Y., Pan, M., Fu, G., Yao, Y., Gao, X., Tang, P., Zhou, Y., et al. (2019) · Europe PMC (PubMed Central) · Cited by 19
Ohki, J., Sakashita, A., Aihara, E., Inaba, A., Uchiyama, H., Matsumoto, M., Ninomiya, Y., Yamane, T., Oishi, Y., & Iwatsuki, K. (2020) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2020.1713043 · Cited by 19
Liu, M., Yu, W. L., Jin, J., Ma, M., Tie-zhu, A., Nie, Y., & Teng, C. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00509.2019 · Cited by 19
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Čtveráčková, L., Jančula, D., Raška, J., Babica, P., & Sovadinová, I. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176069 · Cited by 19
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Zhao, L., Gong, Y.-Q., Wang, Y., Liu, B., Chu, Y., Gui, S., Zheng, Y., & Chen, X. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.791861 · Cited by 19
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Li, C., Chiu, M. C., Yu, Y., Liu, X., Xiao, D., Huang, J., Wan, Z., & Zhou, J. (2022) · Journal of Visualized Experiments · doi:10.3791/63684 · Cited by 19
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Liu, Q., Zeng, A., Liu, Z., Wu, C., & Song, L. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.956244 · Cited by 19
Waddell, S. H., Yao, Y., Olaizola, P., Walker, A., Jarman, E. J., Gournopanos, K., Grãdinaru, A., Christodoulou, E., Gautier, P. E., Boerrigter, M. M., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abq5930 · Cited by 19
Hepatic progenitor cells in canine and feline medicine: potential for regenerative strategies
Kruitwagen, H. S., Spee, B., & Schotanus, B. A. (2014) · BMC Veterinary Research · doi:10.1186/1746-6148-10-137 · Cited by 19
Chikada, H., Ito, K., Yanagida, A., Nakauchi, H., & Kamiya, A. (2015) · Scientific Reports · doi:10.1038/srep14989 · Cited by 19
Raška, J., Čtveráčková, L., Dydowiczová, A., Sovadinová, I., Bláha, L., & Babica, P. (2018) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2018.03.011 · Cited by 19
Yang, L., Wang, S., Qiao, Z., Liu, Y., Wang, X., Liu, L., Yang, C., Ding, J., Lei, M., Zheng, J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-64069-8 · Cited by 20
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Addressing Key Questions in Organoid Models: Who, Where, How, and Why?
Gómez‐Álvarez, M., Agustina‐Hernández, M., Francés‐Herrero, E., Rodríguez‐Eguren, A., Bueno-Fernández, C., & Cervelló, I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242116014 · Cited by 18
Kim, H.-Y., Charton, C., Shim, J. H., Lim, S. Y., Kim, J.-H., Lee, S., Ohn, J. H., Kim, B., & Heo, C. Y. (2024) · Cells · doi:10.3390/cells13090729 · Cited by 18
Effects of a small molecule R-spondin-1 substitute RS-246204 on a mouse intestinal organoid culture
Nam, M.-O., Hahn, S., Jee, J. H., Hwang, T.-S., Yoon, H. S., Lee, D. H., Kwon, M., & Yoo, J. (2017) · Oncotarget · doi:10.18632/oncotarget.23721 · Cited by 18
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Weng, P., Aure, M. H., & Ovitt, C. E. (2019) · Stem Cells · doi:10.1002/stem.3046 · Cited by 18
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Ye, B., Yang, L., Qian, G., Liu, B., Zhu, X., Zhu, P., Ma, J., Xie, W., Li, H., Lu, T., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2019103786 · Cited by 18
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Yan, Y. L., Wang, R., Hu, X., Wang, S., Zhang, L., Hou, C., & Zhang, L. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.07.005 · Cited by 18
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Manohar, R., Li, Y., Fohrer-Ting, H., Guzik, L. J., Stolz, D. B., Chandran, U. R., LaFramboise, W. A., & Lagasse, E. (2015) · Stem Cell Research · doi:10.1016/j.scr.2014.12.003 · Cited by 18
Fukuda, T., Takayama, K., Hirata, M., Liu, Y., Yanagihara, K., Suga, M., Mizuguchi, H., & Furue, M. K. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.02.022 · Cited by 18
Sánchez‐Romero, N., Sainz‐Arnal, P., Plá-Palacín, I., Dachary, P. R., Almeida, H., Pastor, C., Rubio-Soto, D., Rodriguez, M. C., Arbizu, E. O., Martinez, L. B., et al. (2019) · Differentiation · doi:10.1016/j.diff.2019.03.001 · Cited by 18
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van Tienderen, G. S., Willemse, J., van Loo, B., van Hengel, E. V. A., de Jonge, J., van der Laan, L. J. W., Leijten, J., & Verstegen, M. M. A. (2022) · Cells · doi:10.3390/cells11223657 · Cited by 17
Jin, S., Zhu, L., Bao, R., Yang, L., Zhuang, T.-L., Lian, L., Wang, T., Yin, J., Zhang, S., Zhou, L., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-63351-z · Cited by 17
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Kim, H. J., Kim, G., Chi, K. Y., & Kim, J. (2022) · International Journal of Stem Cells · doi:10.15283/ijsc22154 · Cited by 17
Peng, J., Li, F., Wang, J., Wang, C., Jiang, Y., Liu, B., He, J., Yuan, K., Pan, C., Lin, M., et al. (2022) · Cell Discovery · doi:10.1038/s41421-022-00474-3 · Cited by 17
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Chen, J., Horiuchi, S., Kuramochi, S., Kawasaki, T., Kawasumi, H., Akiyama, S., Arai, T., Morinaga, K., Kimura, T., Kiyono, T., et al. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-023-03629-5 · Cited by 17
Zhang, Y., Liu, M., Xie, N., Wang, Z., Yu, C., Li, J., & Zhou, X. (2024) · hLife · doi:10.1016/j.hlife.2024.05.002 · Cited by 17
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Alison, M. R., & Lin, W. (2015) · The Journal of Pathology · doi:10.1002/path.4667 · Cited by 17
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Xu, A. T., Tong, J. L., & Ran, Z. H. (2015) · Journal of Digestive Diseases · doi:10.1111/1751-2980.12305 · Cited by 17
Emerging advancements in liver regeneration and organogenesis as tools for liver replacement
Huppert, S. S., & Campbell, K. M. (2016) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0000000000000365 · Cited by 17
Sun, S., Wang, Y., Wang, J., & Bi, J. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-03061-4 · Cited by 17
Madácsy, T., Varga, Á., Papp, N., Tél, B., Pallagi, P., Szabó, V., Kiss, A. K., Fanczal, J., Rakonczay, Z., Tiszlavicz, L., et al. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04287-1 · Cited by 17
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Anzai, K., Chikada, H., Tsuruya, K., Ida, K., Kagawa, T., Inagaki, Y., Mine, T., & Kamiya, A. (2016) · Scientific Reports · doi:10.1038/srep28283 · Cited by 17
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Hou, C., Sha, W., Xu, Z., Hu, Y., Amakye, W. K., Yao, M., & Ren, J. (2021) · Food Chemistry · doi:10.1016/j.foodchem.2021.131634 · Cited by 16
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Yue, H., Menon, S., Ottakandathil, B. R., Wu, Z., Man-Ting, S., Chung, B., Yuen, W. K. K., Tam, P. K. H., & Hang, L. V. C. (2024) · Toxins · doi:10.3390/toxins16030144 · Cited by 16
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Greggio, C., Franceschi, F. D., & Grapin‐Botton, A. (2014) · Stem Cells · doi:10.1002/stem.1828 · Cited by 16
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Wu, Q., Liu, J., Liu, L., Chen, Y., Wang, J., Leng, L., Yu, Q., Duan, Z., & Wang, Y. (2018) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.8b00652 · Cited by 16
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Rees, W. D., Telkar, N., Lin, D. T. S., Wong, M. Q., Poloni, C., Fathi, A., Kobor, M. S., Zachos, N. C., & Steiner, T. S. (2022) · Cell Reports · doi:10.1016/j.celrep.2021.110283 · Cited by 16
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Zhong, Y., Huang, W., Du, J., Wang, Z., He, J., & Luo, L. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.005568 · Cited by 15
Clark, M. P., Huynh, T., Rao, S., Mackiewicz, L., Mason, H., Romal, S., Stutz, M. D., Ahn, S. H., Earnest, L., Sozzi, V., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03924-0 · Cited by 15
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Lee, J.-Y., Baek, H., Jang, J., Park, J., Cha, S.-R., Hong, S., Kim, J., Lee, J., Hong, I., Wang, S.-J., et al. (2023) · Toxicology in Vitro · doi:10.1016/j.tiv.2023.105585 · Cited by 15
Zdyrski, C., Gabriel, V., Gessler, T. B., Ralston, A., Sifuentes‐Romero, I., Kundu, D., Honold, S. T., Wickham, H., Topping, N. E., Sahoo, D. K., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-05818-1 · Cited by 15
Jabri, A., Khan, J. A., Taftafa, B., Alsharif, M., Mhannayeh, A., Chinnappan, R., Alzhrani, A., Kazmi, S., Mir, M. S., Alsaud, A. W., et al. (2024) · Bioengineering · doi:10.3390/bioengineering11040346 · Cited by 15
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Jung, N., Moreth, T., Stelzer, E. H. K., Pampaloni, F., & Windbergs, M. (2021) · Biomaterials Science · doi:10.1039/d1bm00597a · Cited by 15
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Marx, U., Accastelli, E., David, R. M., Erfurth, H., Koenig, L., Lauster, R., Ramme, A. P., Reinke, P., Volk, H., Winter, A., et al. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.728866 · Cited by 15
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Flanagan, D. J., Schwab, R., Tran, B. M., Phesse, T. J., & Vincan, E. (2016) · Methods in molecular biology · doi:10.1007/7651_2016_14 · Cited by 15
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Kasuga, A., Semba, T., Sato, R., Nobusue, H., Sugihara, E., Takaishi, H., Kanai∥, T., Saya, H., & Arima, Y. (2020) · Cancer Science · doi:10.1111/cas.14703 · Cited by 15
Current experimental human tissue‐derived models for prostate cancer research
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Huang, W., Qiu, B., Qi, X.-S., Chen, C., Liu, W., Zhou, S.-A., Ding, M., Lu, F., Zhao, J., Tang, D., et al. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01123-2 · Cited by 14
Metadata
- Authors
- Huch, M., Dorrell, C., Boj, S. F., van Es, J. H., Li, V. S. W., van de Wetering, M., Sato, T., Hamer, K., Sasaki, N., Finegold, M. J., Haft, A., Vries, R. G., Grompe, M., & Clevers, H.
- Affiliations
- Utrecht University (NL)
- Oregon Health & Science University (US)
- Keio University (JP)
- Baylor College of Medicine (US)
- Corresponding author
- Clevers, Hans
- ORCID
- Venue
- Nature
- Published
- 2013-01-27
- Volume
- 494
- Issue
- 7436
- Pages
- 247-250
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3634804
- OpenAlex
- W2008285918
- Cited by
- 1,555
- References
- 33
- Citations by year
- 2026: 66 · 2025: 117 · 2024: 148 · 2023: 118 · 2022: 122 · 2021: 143 · 2020: 146 · 2019: 120 · 2018: 125 · 2017: 120 · 2016: 109 · 2015: 80 · 2014: 95 · 2013: 43
- FWCI
- 67.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Funders
- Wellcome Trust (104151)
- Japan Society for the Promotion of Science
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK051592, P30DK056338)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- Wnt signaling, liver regeneration, liver organoids, hepatocyte differentiation, bile duct regeneration, tyrosinemia type I, RSPO1, clonal expansion, stem cell transplantation, liver injury, lineage tracing
- MeSH terms
- Alleles, Animals, Bile Ducts, Clone Cells, Culture Media, Disease Models, Animal, Female, Hydrolases, Liver, Liver Diseases, Male, Organoids, Regeneration, Stem Cells, Cell Lineage, Thrombospondins, Tyrosinemias, Hepatocytes, Multipotent Stem Cells, Receptors, G-Protein-Coupled, Mice, Gene Knock-In Techniques, Wnt Signaling Pathway
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